Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Levamisole”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1991

The efficacy of mixtures of albendazole sulphoxide and levamisole against sheep nematodes resistant to benzimidazole and levamisole.

Faecal egg count reduction tests and an anthelmintic efficiency assay were used to assess the efficacy of combinations of albendazole sulphoxide and levamisole against populations of Ostertagia and Trichostrongylus sp. which contained different proportions of worms resistant to both benzimidazole and levamisole anthelmintics. Compared to the effects of either drug alone, significantly greater efficacy was obtained using combinations which included dose rates similar to those recommended for the separate components. At these dose rates, the mixtures reduced mean faecal egg counts by 95% or more, and caused a reduction of 68% in adult Ostertagia sp. and more than 95% for 4th stage Ostertagia and T colubriformis. The increased efficacy of the mixtures could be accounted for by actions of the drugs acting independently.

Albendazole↗
PubMed1999

Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04.

PURPOSE: To compare the efficacy of leucovorin-modulated fluorouracil (FU+LV) with that of fluorouracil and levamisole (FU+LEV) or with the combination of FU+LV and levamisole (FU+LV+LEV). PATIENTS AND METHODS: Between July 1989 and December 1990, 2,151 patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the colon were entered onto National Surgical Adjuvant Breast and Bowl Project protocol C-04. Patients were randomly assigned to receive FU+LV (weekly regimen), FU + LEV, or the combination of FU+LV+LEV. The average time on study was 86 months. RESULTS: A pairwise comparison between patients treated with FU+LV or FU+LEV disclosed a prolongation in disease-free survival (DFS) in favor of the FU+LV group (65% v 60%; P =.04); there was a small prolongation in overall survival that was of borderline significance (74% v 70%; P =.07). There was no difference in the pairwise comparison between patients who received FU+LV or FU+LV+LEV for either DFS (65% v 64%; P =.67) or overall survival (74% v 73%; P =.99). There was no interaction between Dukes' stage and the effect of treatment. CONCLUSION: In patients with Dukes' B and C carcinoma of the colon, treatment with FU+LV seems to confer a small DFS advantage and a borderline prolongation in overall survival when compared with treatment with FU+LEV. The addition of LEV to FU+LV does not provide any additional benefit over and above that achieved with FU+LV. These findings support the use of adjuvant FU+LV as an acceptable therapeutic standard in patients with Dukes' B and C carcinoma of the colon.

Aged↗
PubMed1989

A new pharmacological testing method--different effects of levamisole and the serum of mice orally treated with levamisole on mitogenic activity of lipopolysaccharide.

The direct addition of levamisole to murine splenic lymphocytes had no effect on the mitogenic activity of lipopolysaccharide. However, the addition of serum of mice orally treated with levamisole increased the mitogenic activity, and this increased activity using serum was similar to the result obtained in an in vivo experiment. These results suggest that the new in vitro experimental method using serum may be able to reproduce the in vivo effect of drugs.

Animals↗
PubMed1991

Immunomodulatory action of levamisole--I. Structural analysis and immunomodulating activity of levamisole degradation products.

In our laboratory we observed that solutions of levamisole (LMS) stored at 4 degrees C consistently enhanced the lymphocyte proliferation response to concanavalin A (Con A) more than freshly prepared solutions did. To determine if the increased immunopotentiation observed with the stored solutions of LMS was due to products formed from LMS, we assessed the stability of LMS when stored at 4 or 37 degrees C at pH 6, 7, 7.5 and 8. Analysis of the various solutions by high pressure liquid chromatography demonstrated that LMS decomposes during storage in neutral and alkaline conditions to form three products. The formation of the products was accelerated by increasing the temperature from 4 to 37 degrees C. The three degradation products were purified by preparative high pressure liquid chromatography and their structures determined by mass spectrometry, infrared spectrometry and homo- and heteronuclear two dimensional nuclear magnetic resonance spectroscopy. The degradation products, denoted as No. 1, No. 2 and No. 3, based on their high pressure liquid chromatography retention times, were identified as: No. 1, 3-(2-mercaptoethyl)-5-phenylimidazolidine-2-one; No. 2, 6-phenyl-2,3-dihydroimidazo (2,1-b) thiazole and No. 3, bis [3-(2-oxo-5-phenylimidazolidin-1-yl) ethyl] disulfide. Product 2 significantly enhanced murine lymphocyte proliferation responses to concanavalin A (Con A) at concentrations between 0.5 and 10.0 micrograms/ml (whereas the optimum concentration of LMS is 10-100 fold higher (50-100 micrograms/ml)). Products 1, 2 and 3 significantly inhibited the lymphocyte proliferative response at concentrations greater than 2.2, 10.0 and 10.0 micrograms/ml, respectively. These studies indicate that under relatively mild conditions, including physiological conditions, LMS may decompose to products which inhibit or enhance lymphocyte responses to Con A.

Animals↗
PubMed2003

The role of levamisole in the adjuvant treatment of stage III colon cancer patients: a randomized trial of 5-fluorouracil and levamisole versus 5-fluorouracil alone.

Adjuvant 5-fluorouracil (5FU) and levamisole (Lev) have been considered standard treatment for stage III colon cancer patients. However, the uncertain contribution of Lev to the efficacy of treatment has led many oncologists to prefer the 5FU/leucovorin combination. To establish the role of Lev, we conducted a randomized trial comparing the 5FU/Lev combination with 5FU alone in patients with Dukes' C colon cancer. Patients with stage III colon cancer were randomized to receive 5FU alone (450 mg/m2 i.v. bolus daily for 5 days and then, beginning at day 28, weekly for 48 weeks) or the same plus Lev (50 mg orally three times/day for 3 days, repeated every 2 weeks for 1 year). From December 1994 to March 1998, 92 patients were assigned to receive 5FU/Lev, and 93 were assigned to receive 5FU alone. Leukopenia and hepatic toxicity were more frequent in patients receiving 5FU/Lev as compared with those receiving 5FU (respectively, p = 0.003 and p = 0.039), whereas other toxicities were equivalent and mild in both arms. After a median follow-up time of 48 months, 80 patients have had recurrences (40 in each arm) and no advantages in terms of disease-free survival and overall survival could be demonstrated for the combination arm. The addition of Lev to 5FU does not seem to be relevant for the clinical activity of this adjuvant regimen, whereas toxicity related to Lev should be considered when an adjuvant treatment for stage III colon cancer patients is proposed.

Administration, Oral↗
PubMed1984

Levamisole in postoperative adjuvant immunochemotherapy for gastric cancer. A randomized controlled study of the MMC + Tegafur regimen with or without levamisole. Report I.

The usefulness of LMS in postoperative immunochemotherapy of gastric cancer was investigated. In compliance with the protocol, MMC was given at a dose of 20 mg on the day of gastrectomy, and an additional 10 mg on the next day IV. The patients receiving 600 mg Tegafur daily were then divided into two groups according to whether LMS was also given or not. LMS was administered for 3 days before the operation in a daily dose of 150 mg and for 1 year or more after operation according to a schedule of 3 days' administration followed by an 11-day interval. The 2-year follow-up demonstrated that in stage III patients, the LMS (+) regimen was superior to the LMS (-) regimen, since the former prolonged the relapse-free interval significantly. The survival rate for stage III disease was also significantly higher in the LMS (+) than in the LMS (-) group. There was no significant difference in the incidence of subjective or objective side-effects between two groups. The incidence of agranulocytosis was comparable in the two groups.

Adult↗
PubMed1993

Experimental modulation of IL-1 production and cell surface molecule expression by levamisole.

Data from a variety of sources suggest that one target cell for levamisole might be the macrophage. Current results reveal that oral levamisole pre-treatment provides elicited peritoneal macrophages with the ability to respond better to ex vivo LPS stimulation, and that levamisole can directly act on LPS-stimulated macrophages in vitro, resulting in enhanced production of IL-1, a key mediator of the immune response. These data offer further biological and immunologic evidence that IL-1 production is indeed enhanced by levamisole. Finally, these phenomena were not confined to macrophages taken from mice given levamisole. Increased IL-1 expression was found to occur for cells treated in vitro with levamisole, demonstrating that there were direct effects by levamisole on LPS-stimulated macrophage cytokine production. IL-1 has been reported to have a number of direct and indirect anti-tumor effects which might be sufficient to provide localized protection against tumor invasion or growth in the adjuvant setting. The findings described above are therefore consistent with suggestions of an increased host response in certain types of cancer due to levamisole treatment, and are also consistent with reports of levamisole's providing a beneficial effect in other cases of immunodeficiency disease. Recent clinical data provided by Janik et al. demonstrate that levamisole administration caused increases in circulating levels of neopterin and soluble IL-2 receptor (sIL-2R). This in vivo result is consistent with in vitro data showing augmented IL-1 induction after levamisole treatment, since neopterin is a marker for macrophage activation and sIL-2R release correlates with IL-2 production and binding after IL-1 activation of T-cells. These data are therefore consistent with the hypothesis that levamisole can induce a macrophage-derived cytokine cascade which may have beneficial effects in host responses to human cancer. It is attractive to speculate that there may be increased cytokine expression in vivo (yet to be confirmed) which might contribute to the added clinical benefit when 5-FU is combined with levamisole. Data from nude mice bearing human tumor xenografts demonstrate improved antitumor responses to 5-FU in combination with levamisole, and it will be interesting to determine whether increased interferon, TNF, or other cytokines can be observed in this model. In addition, the ability of levamisole to increase ICAM-1 expression on certain tumor cell lines may be a mechanism by which similar cells are rendered more sensitive to host effector mechanisms in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

A randomized trial comparing cisplatin plus 5-fluorouracil with or without levamisole in operable gastric cancer.

OBJECTIVES: To determine the effectiveness and toxicity when levamisole was added to the adjuvant combination chemotherapy in patients with operable gastric cancer. METHODS: After en bloc resection of gastric cancer without gross or microscopic evidence of residual disease from April 1991 to December 1992, 100 patients were randomized to 6 months of 5-fluorouracil 1,000 mg/m2/day administered as continuous infusion for 5 days, cisplatin 60 mg/m2/day as intravenous infusion for 1 day with or without levamisole (50 mg every eight hours P.O for a period of three days every 2 weeks for 6 months). This chemotherapy treatment was begun within 2 to 4 weeks after the surgery. The chemotherapy consisted of discrete 5-day courses administered at 4-weeks intervals. All 100 patients are assessable. RESULTS: The fifty patients were assigned to each treatment group. There was no statistical difference and no bias in the distribution of characteristics of the 100 evaluable patients between the two groups. A total of 274 courses of treatment were given in the levamisole group and 260 courses of treatment in non-levamisole group. Eleven patients in each group did not finish planned 6 courses of treatment mainly due to non-compliance. At median follow up of 39 months, 32 patients relapsed 19 in the levamisole group and 13 in the non-levamisole group (p = 0.284). Twenty five patients died of relapsed diseases, 15 in the levamisole group and 10 in the non-levamisole group. The levamisole group tended to show more risk of overall death rate and recurrence than the non-levamisole group. However, this result was not statistically significant at 3 years. The treatment was well tolerated in both treatment groups. The grade 2-3 toxicities were nausea/ vomiting (levamisole, non-levamisole group; 31.7%, 29.3% of treatment courses respectively), diarrhea (7.6%, 8.4%), mucositis (11.6%, 12.3%), and leukopenia (9.8%, 9.6%). CONCLUSION: Levamisole had negative effects on disease-free survival and overall survival when added to adjuvant combination chemotherapy of cisplatin and 5-fluorouracil in patients with operable gastric cancer. Both treatment arms were generally well tolerated and the toxicity profile was similar with or without levamisole.

Adjuvants, Immunologic↗
PubMed1992

Comparative neuromuscular blocking actions of levamisole and pyrantel-type anthelmintics on rat and gastrointestinal nematode somatic muscle.

The basis for the comparative toxicity to parasitic nematodes and their mammalian hosts of the anthelmintics levamisole, pyrantel, and several related analogs on somatic nicotinic cholinergic transmission was examined. Measurements of muscle contractility and membrane potential were made using the isolated hemidiaphragm preparation of the rat and isolated axial muscle segments from the gastrointestinal nematode Haemonchus contortus. Pyrantel caused a dose- and time-dependent reduction of nerve-evoked twitches in the rat diaphragm. These effects were exacerbated by increasing the frequency of phrenic nerve stimulation from 0.5 to 50 Hz. Levamisole was less potent and the onset of its effects slower than pyrantel. Neither drug significantly affected twitches evoked from d-tubocurarine-blocked preparations following direct stimulation of the diaphragm. Twitch depression was reversed by washing, but not by application of physostigmine. In H. contortus, both drugs stimulated a spastic contraction and sustained paralysis in the concentration range of 1-10 microM, mimicking the action of nicotine. Neither nicotinic nor muscarinic antagonists blocked these responses. Moreover, neither nicotinic antagonists nor muscarinic agonists or antagonists had any independent effect on contractility of the parasite muscle segments. The blocking actions of levamisole and pyrantel on H. contortus axial muscle were associated with membrane depolarization at the muscle. In the rat-isolated hemidiaphragm, pyrantel, but not levamisole, depolarized end-plate regions of muscle fibers. d-Tubocurarine blocked the depolarizing action of pyrantel but not levamisole on rat-isolated hemidiaphragm. In axial muscle fibers of H. contortus, d-tubocurarine did not block the depolarizing actions of pyrantel, levamisole, or nicotine. 3-Bromo and 3-amino derivatives of levamisole were equipotent with and mimicked the actions of the parent compound on H. contortus axial muscle contractility. In the rat preparation, the 3-bromo derivative was more potent than levamisole or 3-amino-levamisole. 3-Amino-levamisole, but not 3-bromo-levamisole, depolarized muscle end-plate membrane in the rat diaphragm. Results of the present study are consistent with the following conclusions: (a) both levamisole and pyrantel block contractility of nematode axial muscle by causing sustained depolarization of the muscle membrane; (b) both drugs block neuromuscular transmission at the mammalian neuromuscular junction but their mechanisms appear to differ; (c) levamisole and pyrantel are more potent blockers of neuromuscular transmission in H. contortus than in the rat. These results suggest that potentially important pharmacological differences exist between nematode and mammalian somatic nicotinic receptors.

Animals↗
PubMed1992

Levamisole potentiation of fluorouracil antiproliferative activity mimicked by orthovanadate, an inhibitor of tyrosine phosphatase.

BACKGROUND: Levamisole is an effective antihelminthic drug with immunomodulatory and anticancer activities in model systems. Combined with fluorouracil (5-FU) as adjuvant treatment following resection of Dukes' stage C colon carcinomas, levamisole significantly reduces mortality. However, neither 5-FU nor levamisole alone has a significant effect on survival in this patient group. Previously, we noted that in vitro levamisole potentiated the antiproliferative activity of 5-FU. PURPOSE: Because levamisole is known to inhibit alkaline phosphatases and has been reported to inhibit dephosphorylation of some membrane phosphoproteins, we studied the effects of levamisole analogues and of chemically unrelated inhibitors of phosphatases for their ability to potentiate 5-FU inhibition of tumor cell line proliferation in vitro. METHODS: Human cancer cell lines were exposed to drugs alone or in combination with 5-FU. Antiproliferative activity was measured by determining the extent of reduction of colony formation by the cell lines in test plates compared with control plates. RESULTS: We found that potentiation of 5-FU cytotoxicity by levamisole and by p-hydroxytetramisole, a metabolite of levamisole, is mimicked by orthovanadate, an inhibitor of tyrosine phosphatases, but not by okadaic acid, an inhibitor of serine and threonine phosphatases, Furthermore, l-p-bromotetramisole, a synthetic analogue of levamisole that is 10-fold more potent in inhibition of alkaline phosphatase than levamisole, potentiates the antiproliferative activity of 5-FU to a greater extent than d-p-bromotetramisole, a stereoisomer of l-p-bromotetramisole with little antiphosphatase activity. CONCLUSION: Inhibition of tyrosine phosphatases may be responsible for the potentiation by levamisole of the inhibitory activity of 5-FU in vitro. IMPLICATIONS: Inhibition of dephosphorylation of regulatory phosphoproteins may be related to the therapeutic efficacy of the combination of levamisole and 5-FU in the adjuvant treatment of colon carcinoma and may underlie at least some of the multiple effects of levamisole on immune parameters.

Breast Neoplasms↗
PubMed1996

Levamisole effects on major histocompatibility complex and adhesion molecule expression and on myeloid cell adhesion to human colon tumor cell lines.

BACKGROUND: The drug levamisole has been successfully used in combination with fluorouracil to increase the disease-free interval and survival of patients who have undergone surgical resection of Dukes' stage C colon cancer. Levamisole is thought to affect the host immune response. Several recent studies have examined its effect on the expression of major histocompatibility complex (MHC) class I molecules, but the results have been inconsistent. An equally important requirement for a host cellular immune response is the adhesion of leukocytes to tumor cells. The latter may be required for cell-mediated antitumor cytotoxic responses. PURPOSE: We evaluated the ability of levamisole to affect the expression of MHC class I molecules and cell-adhesion molecules and determined whether levamisole could affect leukocyte adhesion to tumor cells that had been treated with the drug. METHODS: A panel of four human colon tumor cell lines (HT-29, SW-620, HCT-15, and LoVo), A-375 human melanoma cells, and human umbilical vein endothelial cells (HUVEC) were cultured in the presence of levamisole and examined by solid-phase enzyme immunoassay to determine the level of expression of MHC class I, intercellular adhesion molecule 1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1), leukocyte integrin VLA-4, and lymphocyte-functional antigen (LFA-1) molecules. Adhesion of HL-60 and THP-1 myeloid cells to tumor cells was also evaluated. Tumor necrosis factor (TNF) at 10 ng/mL was used as a positive control for increasing adhesion molecule expression and cell-cell adhesion. The statistical significance of differences in cell surface molecule expression and functional adhesion between treated and control cells were tested by use of analysis of variance and the two-tailed Dunnett's test. RESULTS: Treatment with levamisole (0.1 and 1 micrograms/mL) caused the levels of MHC class I expression to increase approximately threefold above control levels on HCT-15 and LoVo colon tumor cells (P < .05 in each case) compared with untreated cells, caused minimal increases on HT-29 cells (to 1.5 times control levels), but caused no significant increases on SW-620 colon tumor or A-375 melanoma cells. The HCT-15 and LoVo colon tumor cells had very low basal MHC expression Levamisole (1 micrograms/mL) increased VCAM-1 expression on HT-29 and SW-620 colon tumor cells to 4.3 and 2.4 times (P < .05 in each case) control levels, respectively, doubled ICAM-1 expression on HT-29 cells (P < .05), and increased LFA-1 expression on HT-29, LoVo, and A-375 cells to 2.1, 3.2, and 1.8 (P < .05 in each case) times control levels, respectively. TNF (10 ng/mL) was used as a positive control and yielded increased expression of MHC class I molecules on the HT-29, LoVo, SW-620, and HCT-15 cells (2.5, 7.8, 1.9, and 4.8 times control levels, respectively; P < .05 in each case). TNF increased VCAM-1 expression to 4.2 times the vehicle-treated control levels (P < .05) on HT-29 cells and increased ICAM-1 expression on HT-29, LoVo, and SW-620 cells (8.4, 1.8, and 1.9 times vehicle control levels, respectively; P < .05 in each case). THP-1 and HL-60 cells demonstrated increased adhesion to levamisole-treated HT-29 colon tumor cells. HL-60 cells also exhibited increased levamisole-mediated adherence to LoVo and HCT-15 cells. Adherence by THP-1 was significantly improved after levamisole treatment of the HUVEC, SW-620, and A-375 cells (P < .05 in each case). CONCLUSIONS: Levamisole can directly affect the expression and function of molecules that are engaged in cell-cell recognition and signaling on the surfaces of some tumor cell lines. However, no consistent pattern between cell-adhesion molecule expression, cell-cell adhesion, or levamisole concentration could be discerned.

Adjuvants, Immunologic↗